Incidence of cardiovascular adverse events (AEs) in resected non-small cell lung cancer (NSCLC) patients receiving adjuvant platinum-based chemotherapy: a single institution experience from Wythenshawe Hospital, Manchester, UK

BackgroundPredicting immune-related adverse events (irAEs) in early stage is being emphasized even more. Host response to disease is reflected in serum proteome level and that allows serum proteome level as a new marker to explore response to immunotherapy. With the help of a serum-based proteomics test, Primary Immune Response (PIR), we are accessing the correlations between developing irAEs and immunotherapy in non-small cell lung cancer (NSCLC) patients.MethodsData of 48 consented NSCLC patients with baseline PIR test done within one week prior to the start of immunotherapy were collected. Samples were grouped into either sensitive or intermediate/resistant (not sensitive) by PIR classification. We analyzed the durations from the immunotherapy initiation to the first episode of irAE. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsAmong the 48 NSCLC patients, 19 patients (39%) experienced one or more irAEs with the majority classified as either grade 1 (n=7, 36%) or grade 2 (n=10, 52%). PIR-sensitive group showed no difference in irAE free period compared to PIR-not sensitive (p=0.92, HR=0.95, 95% CI=00.3212 to 2.834). The median ‘Time to first irAE’ were undefined and 24 in PIR-sensitive and PIR-not sensitive, respectively.ConclusionsOur results demonstrated PIR-sensitive patients are not likely to tolerate immunotherapy longer without developing irAEs.

Download Full-text

Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.703893 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lea Daniello ◽

Mariam Elshiaty ◽

Farastuk Bozorgmehr ◽

Jonas Kuon ◽

Daniel Kazdal ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Stage Iv ◽

Palliative Radiotherapy ◽

Small Cell ◽

Small Cell Lung ◽

Treatment Type ◽

Nsclc Patients

IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

Download Full-text

Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel for patients with non-small cell lung cancer who have progressed after platinum-based chemotherapy

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920936882 ◽

2020 ◽

Vol 12 ◽

pp. 175883592093688

Author(s):

Fan Zhang ◽

Di Huang ◽

Lei Zhao ◽

Tao Li ◽

Sujie Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Monotherapy Group ◽

Small Cell Lung ◽

Metastatic Nsclc ◽

Platinum Based Chemotherapy ◽

Paclitaxel Group ◽

Nsclc Patients

Background: Immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for non-small cell lung cancer (NSCLC) patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Methods: The immunotherapy naïve patients with metastatic NSCLC who received anti-PD-1/PD-L1 monotherapy or combined with nab-paclitaxel after prior platinum-based chemotherapy from 2015 to 2018 in PLA General Hospital were identified. The progression-free survival, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed. Results: Of 57 patients, 40 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel. With a median OS follow-up of 16.3 months, the nab-paclitaxel group showed significantly longer OS compared with the immune monotherapy group (median, 28.6 months versus 15.9 months, log-rank p = 0.020). When adjusted by covariates in COX proportional regression model, both the treatment group [ p = 0.009, hazard ratio (HR) 0.361; 95% confidence interval (CI) 0.168–0.773] and performance status ( p = 0.003, HR 0.372; 95% CI 0.192–0.721) demonstrated independent association with the longer OS from combination therapy. In addition, ORR was 23.5% (4/17) in the immune checkpoints inhibitors (ICIs) plus nab-paclitaxel group versus 13.5% (5/37) in immune monotherapy group ( p = 0.439), with a DCR of 88.2% (15/17) and 59.5% (22/37) ( p = 0.034), respectively. The incidence of grade 3/4 adverse events was 23.5% (4/17) in the combination group and 2.5% (1/40) in the immune monotherapy group. Conclusion: PD-1/PD-L1 inhibitor plus nab-paclitaxel resulted in significantly longer OS and higher response versus ICI single agent in metastatic NSCLC patients who have progressed after platinum-based chemotherapy. These findings need to be further explored by prospective studies.

Download Full-text

The Predictive Role of the 53BP1 Pathway in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients (P) Treated with First-Line Platinum-Based Chemotherapy

Annals of Oncology ◽

10.1016/s0923-7534(20)34205-8 ◽

2012 ◽

Vol 23 ◽

pp. ix533

Author(s):

L. Bonanno ◽

C. Costa ◽

M. Majem ◽

A. Gimenez-Capitan ◽

I. Rodriguez ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Platinum Based Chemotherapy ◽

Predictive Role ◽

Nsclc Patients

Download Full-text

Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504019x15755437099308 ◽

2020 ◽

Vol 28 (3) ◽

pp. 237-248

Author(s):

Stefania Nobili ◽

Daniele Lavacchi ◽

Gabriele Perrone ◽

Giulio Vicini ◽

Renato Tassi ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Single Agent ◽

Small Cell ◽

Small Cell Lung ◽

Single Institution ◽

Nsclc Patients ◽

Combination Regimens

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3‐4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.

Download Full-text